The overall goal of this project is to provide information on the mechanisms that control the specification of granule cell fate in the cerebellar cortex. In the proposed research, we will examine, at the cellular and molecular levels, the signals that control the differentiation of precursor cells derived from the external germinal layer (EGL) of the mouse cerebellar cortex, using an in vitro model system developed in our laboratory. Two issues will be addressed. First, we will determine whether growth factors, in particular those with high levels of expression in developing cerebellum (bFGF, NT3 and BDNF) regulate granule cell specification. Second, to provide a genetic analysis of granule cell determination, we will analyze EGL precursor cells from the neurological mutant mouse weaver, an animal with phenotypic defects in granule cell differentiation, including a failure of neurite outgrowth and glial-guided migration.